The adrenergic nervous system appears to exert profound influences on the early, malignant arrhythmias induced by ischemia associated with coronary artery disease and sudden death. However, available information is inconsistent, and the precise role of the autonomic nervous system in their genesis and perpetuation remains elusive. The overall purpose of this research is to delineate the influence of sympathetic input to the heart on these early malignant ventricular arrhythmias by analyzing local electrophysiological and biochemical changes in the heart in vivo. A feline model of coronary occlusion will be utilized, because it exhibits predictible ventricular arrhythmia ensuing soon after coronary occlusion with a consistent onset time, duration and overall associated mortality. Biopsies from normal and ischemic zones of the left ventricle will be obtained simultaneously and fast frozen in liquid nitrogen for radioimmunoassay of cyclic AMP, potentially useful indices of regional, efferent adrenergic activity and compared to changes in corresponding regional, bipolar electrograms from the same zones. Bipolar recordings from epi-, myo- and subendocardial layers of the ischemic and non-ischemic zones will be obtained simultaneously. The waveforms will be analyzed with a high speed computer. Conduction patterns between normal and ischemic tissue will be analyzed on a beat to beat basis in an attempt to localize the origin of premature impulses. Efferent sympathetic nerve stimulation will be utilized in parallel experiments to characterize their simultaneous, as well as separate influences on bipolar regional electrograms, cyclic nucleotide levels and ventricular arrhythmias. The results obtained should aid in the delineation of the role of adrenergic neural influence on the malignant arrhythmias seen during the period early after the onset of ischemia and should help in developing prophylactic measures designed to prevent sudden death in patients with coronary artery disease.